Stereotactic, large-core, needle biopsy using a prone biopsy table and guided by imaging, is now accepted as an alternative to open surgical biopsy for non-palpable breast lesions discovered by mammography. Compared to previous minimally-invasive techniques, such as fine needle aspiration, sufficient tissue is removed to allow for reliable pathology. Surgical confirmation rates of 95% for diagnosis have been reported and the method is considered a safe alternative to surgical biopsy provided that follow- up needle biopsies or surgical biopsies are performed in the case of a subsequent normal breast tissue diagnosis. A normal diagnosis may mean that the original lesion seen on mammography was missed. Inadequate sampling is the primary reason for a normal breast tissue diagnosis following needle biopsies. This occurs in 2 to 10% of procedures. The needle itself may obscure the image of the lesion or the lesion may be difficult to see because of dense breast tissue or the lesion may move from its expected position due to compression artifacts of the stereotactic targeting apparatus. A means of detecting the target lesions, in real time, at the tissue acquisition aperture of the biopsy needle could reduce the occurrence of inadequate sampling and potentially speed up the overall procedure. A fiberoptic Raman spectroscopy probe, deployed through the biopsy needle, is proposed for this purpose. Raman spectroscopy is a particularly good candidate for lesion detection because it is highly sensitive to microcalcifications which are often associated with such lesions. X-ray mammography is the standard procedure for detecting non-palpable breast cancers at their earliest, most-curable stage. Microcalcifications are small, solid deposits of calcium salts, often associated with cancerous lesions, which strongly absorb x-rays and thus show up as high-contrast shadows on mammograms. Their presence may result in a referral for a stereotactic needle biopsy. In Raman spectroscopy these microcalcifications are indicated by strong, sharp, easily distinguished peaks in the optical spectrum of near-infrared light scattered from the tissue. This spectrum also contains broader peaks due to the chemical constituents of tissue. More subtle shifts in the amplitudes of these peaks can indicate the presence or absence of cancer directly. This diagnostic ability of Raman spectroscopy has already been demonstrated in small, ex-vivo, clinical studies. Side-looking Raman needle probes have yet to be demonstrated in-vivo. In Phase I a practical Raman needle probe will be designed, built and tested on ex-vivo breast tissue cores from large-core needle biopsies. In Phase II a full diagnostic system with real-time analysis capability will be built and tested, in-vivo, during stereotactic needle biopsy procedures. If successful, the Phase II instrument will be shown to reduce the occurrence of inadequate tissue sampling and improve the efficiency of sampling sufficiently to reduce the overall time required by these procedures, saving the cost of subsequent biopsy procedures and the attendant patient distress. PUBLIC HEALTH RELEVANCE: This program will develop a fiberoptic Raman spectroscopy probe which will be deployed inside of a stereotactic breast biopsy needle to indicate, in real time, when the tissue acquisition aperture has been correctly positioned next to microcalcifications and/or suspicious tissue which has been previously found through mammography. This system should reduce the number of biopsy samples necessary to retrieve known microcalcifications and minimize potential "misses", defined as a failure to retrieve microcalcifications coupled with a pathology report of normal tissue. The result should be a reduction of both procedure time and patient distress.